EGFR transcript variants: Potential diagnostic biomarker for glioblastoma, IDH-wildtype?
Year: 2025
Type: article
Study design: Observational Study
Abstract: To the Editor: EGFR transcript variants (EGFRtv) have been primarily described in glioblastoma, IDH-wildtype (GBM) defined by histological features, often in close association with EGFR amplification (EGFRamp).1 EGFRamp is one of the diagnostic molecular biomarkers of GBM, along with TERT promoter (TERTp) mutation and combined gain of chromosome 7 with loss of chromosome 10 (+7/−10)2; it has the highest specificity for the integrated diagnosis of GBM.3 Recent data suggest that EGFRvIII, the most frequent type of EGFRtv, may also serve as a highly specific surrogate marker for GBM.4 Herein, we report the frequency and distribution of EGFRtv observed during routine clinical testing of central nervous system (CNS) tumors and further investigate the potential utility of EGFRtv as a diagnostic molecular biomarker for GBM. CNS tumors from unique patients harboring EGFRtv were selected (n = 428) among 4633 unique CNS tumor patients (adult [>18 years]:pediatric; 3.8:1), with valid results by the Mayo Clinic custom amplicon-based targeted neuro-oncology next-generation sequencing (NGS) panel (2018-2022). This panel consists of a 118-gene DNA mutation and an 81-gene RNA fusion/transcript variant subpanel. A single case was tested by Illumina TruSight Oncology 500 High-Throughput NGS assay to assess for tumor mutational burden (TMB). A subset of cases had data for OncoScan CNV Plus chromosomal microarray used to assess for EGFRamp and +7/−10 status (n = 213), and/or Illumina Infinium EPIC v1.0/2.0 methylation array processed using the NCI/Bethesda v.2 classifier (including genome-wide copy number profiles inferred using the R “conumee” package) to evaluate for methylation profile (n = 16). In 3 cases, methylation data were also used to visually assess copy number alterations in non-GBM cases wherein chromosomal microarray data were unavailable. Copy number alterations inferred by methylation array were called based on distinct intensity signal ratio change above 0.1 (gain) or below 0.1 (loss) the baseline.5 Methylation classifier results were interpreted as “match” (superfamily and class calibrated scores ≥ 0.9), “suggestive” (superfamily score ≥ 0.9 and class score 0.5-0.9) and “no match” (superfamily score < 0.9, regardless of class score).
DOI: 10.1093/jnen/nlaf041
Authors: David J Cook, Paul A Decker, Jayson J Hardcastle, Tom M Kollmeyer, Stephanie A Smoley, Matthew D Isaacson, Mallika Gandham, Surendra Dasari, Zied Abdullaev, Kenneth Aldape, Martha Quezado, Patrick J Cimino, Drew W Pratt, Caterina Giannini, Aivi Nguyen, Aditya Raghunathan, Jorge A Trejo-Lopez, Rachael A Vaubel, M Adelita Vizcaino, Cinthya J Zepeda Mendoza, Hussam Al Kateb, Robert B Jenkins, Cristiane M Ida
Institutions: Mayo Clinic, National Cancer Institute, Center for Cancer Research
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4409782437